Accurate navigation is thought to depend on a neural representation of directional heading, which is carried by an ascending circuit of head direction cells located throughout the limbic system. This head direction signal appears to depend critically on the vestibular system, as the head direction signal and navigation abilities are disrupted by vestibular damage. However, vestibular lesions also disrupt other brain signals, such as the place cell signal of hippocampus, and navigation deficits may therefore result from this collateral damage. As a complementary approach, the proposed studies will use otoconia-deficient mice, which have degraded head direction signals, to evaluate the role of the head direction signal in landmark navigation and path integration. The proposed studies will provide important insight into the roles of vestibular signals in neural representations of space and the roles of these representations in navigation. A thorough understanding of the vestibular contribution to the neural and cognitive representations of space may allow new approaches to the treatment of vestibular pathologies. PUBLIC HEALTH RELEVANCE: Disorientation can occur in many pathologies, including dementia, Alzheimer's disease, and drug abuse, among others. Understanding the brain mechanisms that contribute to disorientation will advance our ability to treat or prevent this debilitating component of these disorders.